Prenatal exposure to valproic acid enhances synaptic plasticity in the medial prefrontal cortex and fear memories

The prefrontal cortex has been extensively implicated in autism to explain deficits in executive and other higher brain functions related to cognition, language, sociability and emotion. Hyper-connectivity and hyper-plasticity at the level of the neuronal microcircuit in the medial prefrontal cortex (mPFC) in the valproic acid (VPA) animal model of autism has been suggested. However, the possible alterations at the system levels are not well understood. The present study investigated the basal synaptic transmission and synaptic plasticity in the mPFC in vivo in the VPA rat model of autism. Furthermore, short-term and long-term retention of fear memories were also examined. The findings displayed that paired-pulse facilitation (PPF) and long-term potentiation (LTP), representing short- and long-term synaptic plasticity, were enhanced by the prenatal exposure to VPA. In addition, the short- and long-term fear memories were enhanced. These results suggest that enhanced synaptic plasticity in the mPFC and fear memories might be one of the mechanisms underlying some symptoms of autism. (C) 2012 Elsevier Inc. All rights reserved.